Factor analysis of neuropsychological domains in a preschool clinic.

INTRODUCTION: The clinical practice of preschool neuropsychology assumes that our assessment tools are measuring underlying neuropsychological functions, and that these functions are negatively impacted by early life neurological injury, disease, and disorder. This study hypothesized that general intellectual capacity and specific cognitive skills, both "broad" neuropsychological domains and "specific" subdomains within those broader clusters, would be differentiable in a preschool-age clinical population. METHODS: Using neuropsychological data from 580 children (6 and 71 months) seen for a clinical neuropsychological evaluation in the Preschool and Infant Neuropsychological Testing (PINT) Clinic, exploratory factor analyses (EFA) were conducted. Results: A one-factor model provided a good fit when considering verbal, nonverbal, and adaptive functions. Consideration of one- versus two-factor solutions for broad neuropsychological domains indicated that a 2-factor solution provided a significantly better fit for the data. Factor 1 was defined by motor, language, and nonverbal reasoning abilities; Factor 2 was defined by inhibitory control and attention. Further consideration of specific neuropsychological functions also supported a 2-factor solution. Factor 1 ("thinking") was defined by nonverbal reasoning, receptive language, and expressive language; Factor 2 ("processing") was defined by impulse control, inhibitory control, inattention, visual-motor integration, and visuo-constructional abilities. Motor skills cross-loaded onto both factors. Secondary analyses suggest these models provide the best fit for preschool-aged children with > 70 overall intellectual functioning and no comorbid medical diagnosis. CONCLUSIONS: In a clinical sample of preschool-age children, neuropsychological assessment data appears to assess a general level of intellectual capacity or functioning. Further differentiation between assessing "thinking" (knowledge and reasoning skills) and "processing" (cognitive attention and processing of information) can be considered clinically. Next steps include more recent clinical sample replication, consideration of whether neuropsychological profiles are detectable in the preschool-age range and whether the results of early life assessment are predictive of future functioning.

Competency-based assessment in clinical neuropsychology at the post-doctoral level: Stages, milestones, and benchmarks as proposed by an APPCN work group.

Objective: In recent years, there has been considerable progress in developing competencies in Clinical Neuropsychology. The field also needs to work towards consistency in competency-based assessment of the development of each competency to ensure competent, independent practice. The purpose of this manuscript is to a) document the relevant literature, b) describe the process applied by an Association of Post-Doctoral Programs in Clinical Neuropsychology (APPCN) workgroup on Competency-Based Assessment, and c) propose a framework and assessment tool for competency-based assessment at the post-doctoral training level. Methods: The work group conducted a literature review of competency-based assessment in Clinical Neuropsychology and related fields, considered various constructs for assessment, delineated a framework that can be flexible for program-specific goals, and created a tool for assessment. The workgroup then asked for review of the framework and assessment tool by APPCN Board of Directors, the APPCN Executive Committee, and Program Directors from APPCN and non-APPCN programs. Revisions were made following this review. Conclusions: This manuscript and proposed assessment tool invite constructive feedback within the community for ongoing evolution of the process and the tool. The proposed assessment tool is intended to be implemented flexibly within post-doctoral programs to respect their specific training goals while simultaneously providing underlying consistency in the method of assessing a recently proposed set of competencies within Clinical Neuropsychology. Creation of competency-based assessment tools across all training levels within Clinical Neuropsychology that facilitate continuity and hierarchical development is a long-term goal.

Fostering equity in education and academic outcomes in children with sickle cell disease.

ObjectiveChildren with Sickle Cell Disease (SCD), who are predominantly Black, face academic disparities in part because of the impact of longstanding racially biased education systems. Adverse systemic factors in addition to neurologic complications put children with SCD at risk for poor academic outcomes. Providing caregivers with information on how to select quality schools and advocate for their child's specific educational needs may influence academic outcomes and reduce educational disparities. We aimed to provide information to caregivers of children with SCD on school selection/quality, enrollment, and special education options.MethodsForty-six caregivers of children with SCD between the ages of 2 and 5:11 years participated in a structured informational session. Caregivers' sense of empowerment regarding educational options for their child was assessed via survey before and after the structured informational session.ResultsCaregivers reported feeling more informed and empowered following their participation in an informational session on school selection/quality, enrollment, and special education options for their child than before the informational session.ConclusionsIt is essential that families of children with SCD have the knowledge, skills, and sense of empowerment to access quality schools beginning in early childhood. Future research will determine if this intervention will improve children's access to academic support and academic outcomes. We theorize improvements in academic outcomes along with addressing systemic disparities may ultimately create a positive impact on vocational and quality of life outcomes in the lives of children with SCD.

Sociodemographic disparities in fetal surgery for myelomeningocele: a single-center retrospective review.

OBJECTIVE: Fetal surgery for myelomeningocele has become an established treatment that offers less risk of requiring a ventricular shunt and improved functional outcomes for patients. An increasing body of literature has suggested that social determinants of health have a profound influence on health outcomes. The authors sought to determine the socioeconomic and racial and ethnic backgrounds of patients who were treated with fetal surgery versus those who underwent postnatal repair. METHODS: Demographic data, the method of myelomeningocele repair, insurance status, and zip code data for patients entered into the National Spina Bifida Patient Registry (NSBPR) from Children's Wisconsin were collected. The zip code was used to determine the Distressed Communities Index (DCI) score, a composite socioeconomic ranking with scores ranging from 0 (no distress) to 100 (severe distress). The zip code was also used to determine the median household income for each patient based on the US Census Bureau 2013-2017 American Community Survey 5-year estimates. RESULTS: A total of 205 patients were identified with zip code and insurance data. There were 23 patients in the fetal surgery group and 182 patients in the postnatal surgery group. All patients were born between 2000 and 2019. Patients in the fetal surgery group were more likely to have commercial insurance (100% vs 52.2%, p < 0.001). Fetal surgery patients were also more likely to be non-Hispanic White (95.7% vs 68.7%, p = 0.058), just missing the level of statistical significance. Patients who underwent fetal surgery tended to reside in zip codes with a higher median household income (mean $66,507 vs $59,133, p = 0.122) and less-distressed communities (mean DCI score 31.3 vs 38.5, p = 0.289); however, these differences did not reach statistical significance. CONCLUSIONS: Patients treated with fetal surgery were more likely to have commercial insurance and have a non-Hispanic White racial and ethnic background. The preliminary data suggest that socioeconomic and racial and ethnic disparities may exist regarding access to fetal surgery, and investigation of a larger population of spina bifida patients is warranted.

Differential access to neuropsychological evaluation in children with perinatal complications or autism spectrum disorder: Impact of sociodemographic factors.

OBJECTIVE: Early childhood evaluation can identify deficits related to disruptions in early brain development and facilitate interventions. Access to care may differ by race/ethnicity or socioeconomic status. We explored neuropsychological evaluation access patterns and examined potential sociodemographic disparities in evaluation timing. Method: Participants were 213 children (age: M = 46.4 months, SD = 15.3 months) with a history of disrupted neural development due to perinatal complications (PC; n = 109) or autism spectrum disorder (ASD; n = 104). We used chi square tests of independence and one-way ANOVAs to compare groups on sociodemographics, referral sources, and cognition. Clinical sample means for cognitive and adaptive variables were compared to normative means to determine the presence of developmental delays. Differences in age at evaluation by race/ethnicity, caregiver education, and referral source, accounting for cognition, were explored with ANCOVAs. Results: The ASD group included significantly more White children and the PC group relatively more Black/African Americans. Children with ASD were referred by primary care physicians and caregivers/school staff; those with PC were referred by other medical providers. All participants performed more poorly than expected across all intellectual and adaptive domains, with greater delays in the ASD group. Children of caregivers with lower education were evaluated earlier in the PC group. For ASD, participants referred by primary care physicians were evaluated earlier. Conclusions: Children with PC and ASD exhibit cognitive delays and require neuropsychological evaluation. Disparities in access to care exist, particularly for minority children with ASD. Ways to promote equal access are discussed.

Disruption of Trim9 function abrogates macrophage motility in vivo.

The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune system during the first few weeks of life. Zebrafish larvae were exposed to immune agonists for various lengths of time, and a microarray transcriptome analysis was executed. This strategy identified known immune response genes, as well as genes with unknown immune function, including the E3 ubiquitin ligase tripartite motif-9 (Trim9). Although trim9 expression was originally described as "brain specific," its expression has been reported in stimulated human Mϕs. In this study, we found elevated levels of trim9 transcripts in vivo in zebrafish Mϕs after immune stimulation. Trim9 has been implicated in axonal migration, and we therefore investigated the impact of Trim9 disruption on Mϕ motility and found that Mϕ chemotaxis and cellular architecture are subsequently impaired in vivo. These results demonstrate that Trim9 mediates cellular movement and migration in Mϕs as well as neurons.

Taxonomy for Education and Training in Clinical Neuropsychology: past, present, and future.

OBJECTIVE: Historically, the clinical neuropsychology training community has not clearly or consistently defined education or training opportunities. The lack of consistency has limited students' and trainees' ability to accurately assess and compare the intensity of neuropsychology-specific training provided by programs. To address these issues and produce greater 'truth in advertising' across programs, CNS, with SCN's Education Advisory Committee (EAC), ADECN, AITCN, and APPCN constructed a specialty-specific taxonomy, namely, the Taxonomy for Education and Training in Clinical Neuropsychology. The taxonomy provides consensus in the description of training offered by doctoral, internship, and postdoctoral programs, as well as at the post-licensure stage. Although the CNS approved the taxonomy in February 2015, many programs have not adopted its language. Increased awareness of the taxonomy and the reasons behind its development and structure, as well as its potential benefits, are warranted. METHODS: In 2016, a working group of clinical neuropsychologists from the EAC and APPCN, all authors of this manuscript, was created and tasked with disseminating information about the taxonomy. Group members held regular conference calls, leading to the generation of this manuscript. RESULTS: This manuscript is the primary byproduct of the working group. Its purpose is to (1) outline the history behind the development of the taxonomy, (2) detail its structure and utility, (3) address the expected impact of its adoption, and (4) call for its adoption across training programs. CONCLUSIONS: This manuscript outlines the development and structure of the clinical neuropsychology taxonomy and addresses the need for its adoption across training programs.

The relationship of neuropsychological functioning to adaptation outcome in adolescents with spina bifida.

Adolescents with spina bifida (SB) vary in their ability to adapt to the disease, and it is likely that numerous risk and protective factors affect adaptation outcomes. The primary aim was to test neuropsychological impairment, exemplified herein by executive dysfunction, as a risk factor in the Ecological Model of Adaptation for Adolescents with SB. Specific hypotheses were that: (1) executive functioning predicts the adaptation outcome of functional independence in adolescents with SB; (2) executive functioning mediates the impact of neurological severity on functional independence; and (3) family and adolescent protective factors are related to functional independence and moderate the relationship between executive functioning and functional independence. Forty-three adolescents aged 12-21 years completed neuropsychological measures and an interview that assessed risk, adolescent and family protective factors, and functional independence. Age, level of lesion, executive functioning, and the protective factor adolescent activities were significantly correlated with the functional independence outcome. In hierarchical regression analysis, the model accounted for 61% of the variance in functional independence outcomes. Executive functioning mediated the impact of neurological severity on functional independence.

The medaka novel immune-type receptor (NITR) gene clusters reveal an extraordinary degree of divergence in variable domains.

BACKGROUND: Novel immune-type receptor (NITR) genes are members of diversified multigene families that are found in bony fish and encode type I transmembrane proteins containing one or two extracellular immunoglobulin (Ig) domains. The majority of NITRs can be classified as inhibitory receptors that possess cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). A much smaller number of NITRs can be classified as activating receptors by the lack of cytoplasmic ITIMs and presence of a positively charged residue within their transmembrane domain, which permits partnering with an activating adaptor protein. RESULTS: Forty-four NITR genes in medaka (Oryzias latipes) are located in three gene clusters on chromosomes 10, 18 and 21 and can be organized into 24 families including inhibitory and activating forms. The particularly large dataset acquired in medaka makes direct comparison possible to another complete dataset acquired in zebrafish in which NITRs are localized in two clusters on different chromosomes. The two largest medaka NITR gene clusters share conserved synteny with the two zebrafish NITR gene clusters. Shared synteny between NITRs and CD8A/CD8B is limited but consistent with a potential common ancestry. CONCLUSION: Comprehensive phylogenetic analyses between the complete datasets of NITRs from medaka and zebrafish indicate multiple species-specific expansions of different families of NITRs. The patterns of sequence variation among gene family members are consistent with recent birth-and-death events. Similar effects have been observed with mammalian immunoglobulin (Ig), T cell antigen receptor (TCR) and killer cell immunoglobulin-like receptor (KIR) genes. NITRs likely diverged along an independent pathway from that of the somatically rearranging antigen binding receptors but have undergone parallel evolution of V family diversity.

The clinical picture of depression in preschool children.

OBJECTIVE: To investigate the clinical characteristics of depression in preschool children. METHOD: One hundred seventy-four subjects between the ages of 3.0 and 5.6 years were ascertained from community and clinical sites for a comprehensive assessment that included an age-appropriate psychiatric interview for parents. Modifications were made to the assessment of major depressive disorder (MDD) criteria so that age-appropriate manifestations of symptom states could be captured. Typical and "masked" symptoms of depression were investigated in three groups: depressed (who met all MDD criteria except duration criterion), those with nonaffective psychiatric disorders (who met criteria for attention-deficit/hyperactivity disorder and/or oppositional defiant disorder), and those who did not meet criteria for any psychiatric disorder. RESULTS: Depressed preschool children displayed "typical" symptoms and vegetative signs of depression more frequently than other nonaffective or "masked" symptoms. Anhedonia appeared to be a specific symptom and sadness/irritability appeared to be a sensitive symptom of preschool MDD. CONCLUSIONS: Clinicians should be alert to age-appropriate manifestations of typical MDD symptoms and vegetative signs when assessing preschool children for depression. "Masked" symptoms of depression occur in preschool children but do not predominate the clinical picture. Future studies specifically designed to investigate the specificity and sensitivity of the symptoms of preschool depression are now warranted.

Preschool major depressive disorder: preliminary validation for developmentally modified DSM-IV criteria.

OBJECTIVE: To investigate the validity of developmentally modified DSM-IV criteria for preschool major depressive disorder (MDD). METHOD: Subjects between the ages of 3.0 and 5.6 years were ascertained from community and clinical sites for a comprehensive assessment that included an age-appropriate psychiatric interview with the parent about the child. Minor developmental modifications to the formal DSM-IV MDD criteria were tested, including translations of symptoms to describe age-appropriate manifestations and setting aside the duration criterion. Preschool children who met modified criteria were compared with psychiatric and normal control groups. RESULTS: Validation for the modified criteria was supported by a specific and stable symptom constellation, social impairment, greater family histories of affective disorders, and higher child-reported symptoms of depression on an age-appropriate puppet interview. Preschool children with MDD displayed "typical" symptoms of depression, as well as vegetative signs. Standard DSM-IV criteria failed to capture 76% of children who met these modified criteria. CONCLUSIONS: Evidence that preschool children can manifest typical symptoms of MDD when age-adjusted symptoms states are assessed is provided. Findings also suggest that standard DSM-/V criteria may not be sufficiently sensitive for preschool children, as they failed to capture a substantial proportion of symptomatic children. Minor modifications to DSM-IV criteria are recommended to capture clinically significant preschool MDD.

Visual attention in preschool children prenatally exposed to cocaine: implications for behavioral regulation.

The presence of cocaine during the prenatal period disrupts the development of neural systems involved in mediating visual attention; therefore, it is possible that prenatal cocaine exposure results in impairments in visual attention in early childhood. In the current study we hypothesized that preschool children with prenatal cocaine exposure would exhibit difficulties in the disengagement operation of visual attention and in sustaining attention, particularly for targets presented in the right visual field. Fourteen cocaine-exposed children and 20 control children between 14 and 60 months of age were assessed on measures of visual attention, cognition, and behavior. Cocaine-exposed children had slower reaction times on disengagement trials in the second half of our attention task, supporting our hypotheses that impairments in disengagement and sustained attention are associated with prenatal cocaine exposure. There was a trend for slower reaction times to targets presented in the right visual field, but not to targets presented in the left visual field. Cocaine-exposed children also exhibited greater difficulties in behavioral regulation. Overall, our findings suggest that children with prenatal cocaine exposure demonstrate specific impairments in visual attention and behavioral regulation.